The applicant's long-term research objectives are to understand the interdependent relationship between the neural control of multi-joint movements and the mechanical design of the human motor system, and to understand how injury to either of these systems compromises normal motor function. The focus of this particular study is on the stretch reflex contributions to the regulation of human arm mechanics, and how this spinally mediated regulation is altered following stroke. Approximately 400,000 Americans suffer their first stroke each year, and this number is expected to exceed 1,000,000 by the year 2050. Cerebral vascular injuries such as stroke can result in a variety of movement related disorders including muscular weakness, abnormal motor synergies and spasticity. Many of these motor disorders are thought to arise from changes in the behavior of spinal circuits contributing to motor behavior; however, few studies have examined the effect of these changes on the coordination of whole limb function. This study seeks to fill this void by using estimates of limb impedance and the stretch reflex contributions to this impedance to quantify changes in the regulation of multi-joint arm mechanics following stroke. The specific aims are (1) to examine the reflex contributions to whole limb stiffness regulation in able-bodied individuals maintaining arm posture, (2) to quantify the changes in whole limb stiffness regulation and the spinal contributions to this regulation following stroke, and (3) to examine the possible mechanisms by which tizanidine, a promising drug for restoring motor function following stroke, alters multi-joint reflex behavior. For all aims, limb mechanics will be quantified using estimates of arm limb impedance, which describes the dynamic relationship between externally imposed displacements of limb posture and the forces generated in response. Impedance will be quantified in all degrees of freedom (DOFs) relevant to normal motor function using a 6 DOF robotic manipulator to perturb arm posture and a 6DOF load cell to measure the corresponding forces in all DOF relevant to normal function. Measurements will be made in able-bodied individuals and in individuals who have suffered a stroke. A small, complementary animal study will be performed to investigate possible mechanisms underlying the actions of tizanidine. [unreadable] [unreadable]